Formulation and Characterization of Solid Lipid Nanoparticles for Topical Delivery of Antibacterial Drug

Introduction

Ciprofloxacin is a therapeutically important antibacterial agent that has been widely used in clinics for a variety of serious fungal infections [1]. The drug may be given orally or intravenously. The oral bioavailability depends upon several factor including aqueous solubility, drug permeability, dissolution rate, first pass metabolism and susceptibility to efflux mechanisms. An interesting alternative approach for ITZ encapsulation may be the use of solid lipid nanoparticles (SLNs) owing to their application for several drugs for topical therapy of fungal skin diseases [2, 3, 4]. The SLNs offered a great potential for the administration of active molecules and simultaneously improved their therapeutic efficacy with great feasibility of incorporation of lipophilic and hydrophilic drugs, enhanced their physical stability, low cost compared to liposomes and ease of scale-up and manufacturing [5, 6, 7, 8]. Moreover, their lipid core made from physiological lipids having high biocompatibility and biodegradability with their potential in epidermal targeting, follicular delivery and controlled release of active moiety with increased skin hydration due to greater occlusivity have been very well established [9, 10].

Material and Method

Ciprofloxacin was obtained from Alpha pharmaceuticals Hyderabad; Stearic acid was purchased from Central Drug House (P) Ltd. New Delhi; Di methyl formamide were purchased from Merck Specialties Private Limited Worli Mumbai; all other required chemicals were procured from supplier. To prepare SLNs dispersion, CPFR, Stearic acid, of different compositions Table 1 were dissolved in 10 ml mixture of Di methyl formamide. Organic solvents were completely removed using a rotary evaporator (Laborota 4000, Heidolph, Germany) to form a drug-embedded lipid layer. This layer was melted by heating at 65°C above the melting point of the lipid. Aqueous phase was prepared by dissolving poly vinyl alcohol (PVA) (2% w/v) in double distilled water (10 ml) and heated to same temperature of oil phase. The hot aqueous phase was added to the oil phase and homogenization was performed (at 2500 rpm and 70°C) using a mechanical stirrer for 30 minutes. The coarse oil in water microemulsion so obtained was sonicated using bath soincator for 25 minutes. ITZ loaded SLN was finally obtained by allowing the hot nanoemulsion to cool at room temperature [11].

Result and Discussion

Particle size and zeta potential for topical administration, irritation and wash out may occur on administration of large-sized particles, since smaller particles are better tolerated [11, 12]. Very small particles as nanoparticles possess adhesive properties, which could prolong the release of the drug in the skin, prevent wash out, and increase bioavailability. The zeta potentials of the drug- loaded SLN presented in Table 2 indicate very stable particles. 1.0% ITZ showed the highest absolute zeta potential, it possessed higher crystallinity, lower drug load and higher particle size than other drug-containing SLN. These factors coupled with the tendency to agglomerate eliminate it from being the best SLN in this study.

Encapsulation efficiencies above 60% were recorded for the SLN batches the high drug loading was also contributed by the behavior of ITZ shows thermo tropic liquid crystalline behavior and may participate in the microstructure of the system. The encapsulation efficiencies obtained for the drug- loaded SLN are presented in Table 3. This was due to complex formation between lipid and the drug, and the participation of drug in the structures formed at the particle surface.

DSC was used to underline the high drug encapsulation potency of the SLN [13]. The higher the enthalpy of the transitions, the more crystalline the SLN and consequently, the more difficult it will be for any drug to be encapsulated.

The DSC result is presented in Figure 1. This showed a slight endothermic signal at about 50℃, confirming their crystallinity [14]. Drug release shows the release profile of ITZ in phosphate buffer (pH 6.8) using dialysis membrane as the release barrier. There was burst release of ITZ from SLNs formulated within the first 125 min. This was due to the more crystalline nature of this SLN, which resulted in more drugs in the periphery and bulk aqueous medium than in the core of the lipid nanoparticles [15, 16]. The profiles of the lipid containing SLN revealed sustained release of the active with regards to topical delivery. Higher quantity of ITZ was released in the batch loaded with higher amount of ITZ.

Conclusion

The high encapsulation efficiency achieved with this novel SLNs formulation indicates this SLN could be an effective drug delivery system for topical active drugs. ITZ- containing SLNs evaluated in this work showed that the performance of their antibacterial application could be improved by formulation as SLN. The studies revealed that the prepared SLNs could be used as a potential carrier for the topical delivery of Ciprofloxacin.